The field of the present invention relates to magnetic resonance imaging. In particular, methods are disclosed herein for functional magnetic resonance imaging.
A wide variety of techniques have been developed for magnetic resonance imaging (MRI); some are also suitable for so-called functional magnetic resonance imaging (fMRI). Some examples are disclosed in:                U.S. Pat. No. 6,271,665 entitled “Extra slice spin tagging (EST) magnetic resonance imaging for determining perfusion” issued Aug. 7, 2001 to Berr et al;        U.S. Pat. No. 6,307,368 entitled “Linear combination steady-state free precession MRI” issued Oct. 23, 2001 to Vasanawala et al;        U.S. Pub. No. 2004/0092809 entitled “Methods for measurement and analysis of brain activity” published May 13, 2004 to DeCharms;        U.S. Pat. No. 6,922,054 entitled “Steady state free precession magnetic resonance imaging using phase detection of material separation” issued Jul. 26, 2005 to Hargreaves et al;        U.S. Pat. No. 7,096,056 entitled “Functional magnetic resonance imaging using steady state free precession” issued Aug. 22, 2006 to Miller et al;        U.S. Pat. No. 7,567,081 entitled “Magnetic resonance non-balanced-SSFP method for the detection and imaging of susceptibility related magnetic field distortions” issued Jul. 28, 2009 to Bieri et al;        Scheffler and Hennig; Is TrueFISP a Gradient-Echo or a Spin-Echo Sequence?; Magnetic Resonance in Medicine 49:395-397 (2003);        Scheffler et al; Detection of BOLD changes by means of a frequency-sensitive true FISP technique: preliminary results; NMR in Biomedicine 14:490-496 (2001);        Scheffler et al; Principles and applications of balanced SSFP techniques; Eur. Radiol. 13:2409-2418 (2003);        Ogawa et al; Brain magnetic resonance imaging with contrast dependent on blood oxygenation; Proc. Natl. Acad. Sci. 87:9868-9872 (1990);        Ogawa et al; “Intrinsic signal changes accompanying sensory stimulation: Functional brain mapping with magnetic resonance imaging,” Proc. Natl. Acad. Sci. 89:5951-5955 (1992);        Kwong et al; Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation; Proc. Natl. Acad. Sci. 89:5675-5679 (1992); and        Jongho Lee; Advanced fMRI Techniques: Steady-State Free Precession Techniques; 19th Annual Meeting & Exhibition, ISMRM, (2011).        
Functional MRI (fMRI) is a general term for MRI methods that are used for mapping the brain activity based on the blood flow (i.e., hemodynamic response) in different regions of the brain. BOLD (Blood Oxygenation Level Dependent) is the fundamental contrast mechanism of most fMRI techniques. BOLD generates functional contrast (between a resting state and an active state) based on the level of oxygenation in the blood perfusing a given region of brain tissue, which in turn slightly changes the magnetic susceptibility of that region of brain tissue. The generated functional contrast is typically quite small, so that typically repetitive scanning and statistical methods are needed to achieve an acceptable signal-to-noise ratio (SNR).
As noted by Miller et al (U.S. Pat. No. 7,096,056): “The dominant method for fMRI, Blood Oxygenation Level Dependent (BOLD) imaging is sensitive to changes in blood oxygenation that occur in response to brain activity. See, for example, Ogawa et al., ‘Intrinsic Signal Changes Accompanying Sensory Stimulation: Functional Brain Mapping With Magnetic Resonance Imaging,’ Proc Natl Acad Sci, USA, 89:5951 5955, 1992. The BOLD method is based on the sensitivity of the MR signal to deoxyhemoglobin, which has a resonance frequency that is shifted relative to water. BOLD fMRI uses Gradient Recalled Echo (GRE) imaging with a long echo time (TE) to increase the signal dephasing due to the deoxyhemoglobin frequency shift, resulting in signal levels that depend on the concentration of deoxyhemoglobin in the blood. While BOLD imaging represents a major advance in brain mapping, this method has a number of important limitations including poor spatial resolution, low signal levels, limited contrast and severe image artifacts. These limitations derive from the fact that BOLD contrast is coupled to sources of image degradation and signal loss.”
Miller et al proceed to disclose “Functional magnetic resonance imaging using steady state free precession” (in U.S. Pat. No. 7,096,056). That method shall be referred to as “conventional BOSS” (Blood Oxygenation by Steady State). The conventional BOSS method takes advantage of the generally high sensitivity of steady-state free precession (SSFP) methods to shifts of resonance frequency. In conventional BOSS, the RF center frequency is adjusted to be between the respective resonance frequencies of oxy- and deoxy-hemoglobin to substantially increase the functional image contrast (between resting and active states of brain tissue) and signal-to-noise ratio by effectively “flipping the signs” of the respective steady-state signals relative to each other (due to a π phase shift across the resonance). An important disadvantage of the conventional BOSS method is the limited extent of the spatial region that can be imaged. That limitation is imposed by practical limitations on the magnetic field uniformity that can be achieved by shimming a real imaging system. In an imaging system with a well-shimmed magnet, inhomogeneities in the magnetic field will typically shift resonance frequencies on the order of 0.1-1.0 Hz per mm across an image. Because the resonance frequency shift between oxy-hemoglobin and deoxy-hemoglobin is only about 5-10 Hz (in a 1.5 or 3 T scanner), the functional image contrast can vary widely over only a few centimeters of the image based on whether the respective resonances have nearly the same phase (little or no contrast) or phases differing by about π (larger contrast). This represents a significant limitation on the utility of the conventional BOSS method, because it is suitable for mapping only relatively small areas of the brain (e.g., regions only a few centimeters wide, over which the RF central frequency lies between the respective resonance frequencies of oxy- and deoxy-hemoglobin). Miller et al suggest RF phase cycling (to increase the spatial extent of the effective mapping) as a solution, but that requires repeated image acquisitions. Such repeated acquisitions are time consuming and may not be suitable for functional imaging in which temporal evolution of the image is desired.